Exploration of the biochemical mechanisms whereby malignant cells alter and migrate into the host's connective tissue structures is the basis of this proposal. Our studies on rabbit V2 carcinoma suggest that collagenase and hyaluronic acid may be significant components of invasive behavior of this neoplasm. We plan to extend these observations in invasive and non-invasive forms of V2 carcinoma. We will search for local and humoral factors regulating the synthesis of hyaluronate and degradative enzymes. In particular we expect to obtain more definitive evidence that these constituents do or do not contribute significantly to the invasive process.